Evidence map›Paper›PMID 41664207›Full record

ArticleClinical epigenetics2026

Integrative multi-omics analysis of macrophage polarization-related genes in atherosclerosis development.

Jinying Gao, Peng Huang, Yibing Zhang

Abstract read
In one paragraph

Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Jinying GaoDepartment of Respiratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun, 130021, China.
Peng HuangSchool of Agroforestry and Medicine, The Open University of China, Beijing, 100081, China.
Yibing ZhangDepartment of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, 130021, China. zhangyibing220@jlu.edu.cn.

Funding

Natural Science Foundation of Science and Technology Department of Jilin Province YDZJ202201ZYTS105the Medical and Health Talent Special Project of Jilin Province JLSRCZX2025-129
6 · The paper itself

Abstract

backgroundThe differentiation of macrophages into foam cells is a hallmark of atherosclerotic plaques, and macrophage polarization is a key driver of disease progression, yet the underlying genetic mechanisms remain poorly understood. We employed summary data-based Mendelian randomization (SMR) combined with transcriptomic validation to explore causal relationships and validate findings at the tissue level.

methodsWe integrated multi-omics data, including DNA methylation (mQTLs), gene expression (eQTLs), and protein expression (pQTLs), from GeneCards and GWAS summary statistics from FinnGen and UK Biobank. SMR and colocalization analyses were used to identify causal associations. Tissue-specific validation was conducted using eQTL data from artery tissues, and transcriptome analysis was performed using GEO datasets to confirm gene expression patterns in atherosclerotic tissues, followed by confirmation in clinical samples. The function of key genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

resultsSMR and colocalization analyses identified 41 methylation sites, 2 genes (DNMT3A and DLGAP5), and 1 protein associated with atherosclerosis. Specifically, methylation site cg10130446 in DLGAP5 was negatively correlated with atherosclerosis, while sites cg08485187 and cg17742416 in DNMT3A were positively associated. Tissue-specific validation revealed that SIRT6 gene expression was linked to atherosclerosis risk in aortic and tibial artery tissues. Transcriptome analysis from GEO database and blood samples confirmed elevated DLGAP5 and SIRT6 expressions.

conclusionsThis study integrates SMR with transcriptomic validation to reveal causal links between macrophage polarization-related genes and atherosclerosis. Key genes DNMT3A, DLGAP5, and SIRT6 were identified as significant candidate regulatory factors. Tissue-specific validation and GEO-based transcriptome analysis provided robust evidence supporting these findings, highlighting the importance of macrophage polarization in atherosclerosis pathogenesis and offering new insights for therapeutic intervention.

Indexed as

AtherosclerosisMacrophagesDNA (Cytosine-5-)-MethyltransferasesDNA MethylationGene Expression ProfilingGenome-Wide Association StudyHumansMendelian Randomization AnalysisMultiomicsQuantitative Trait LociDNA (Cytosine-5-)-MethyltransferasesAtherosclerosisColocalizationMacrophage polarizationMendelian randomization analysisMulti-omics

Identifiers

PMID41664207
PMCPMC12961815

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.